The Take Home

The Take Home: TCT

The annual Transcatheter Cardiovascular Therapeutics Scientific Symposium, held Sept. 21 to 25 in San Diego, brought many of interventional cardiology’s hottest topics to the forefront.

Cardiology Today’s Intervention was on-site and spoke with experts for their perspective on the top research presented at this year’s meeting. Those who provided their opinion included Chandan Devireddy, MD, FACC, FSCAI, from Emory University; C. Michael Gibson, MD, MS, from Harvard Medical School and Beth Israel Deaconess Medical Center; David E. Kandzari, MD, from Piedmont Heart Institute; Cardiology Today’s Intervention Editorial Board Member Ajay Kirtane, MD, SM, from NewYork-Presbyterian Hospital/Columbia University Irving Medical Center; Dharam J. Kumbhani, MD, SM, from UTSouthwestern Medical Center; Cardiology Today’s Intervention Editorial Board Member Sunil V. Rao, MD, from Duke University Health System; Molly Szerlip, MD, FACC, FACP, FSCAI, from Baylor Scott and White The Heart Hospital – Plano; Vinod H. Thourani, MD, FACS, FACC, from MedStar Heart and Vascular Institute; and B. Hadley Wilson, MD, FACC, from Atrium Health and the University of North Carolina School of Medicine.

COAPT

Ajay Kirtane

Kirtane: We heard the results of the COAPT trial. It’s pretty amazing to see results like this, where you see not only reductions in terms of hospitalizations for HF (HR = 0.53; 95% CI, 0.4-0.7) in these 614 patients that have HF with mitral regurgitation treated with MitraClip (Abbott), but also an endpoint of all-cause mortality being decreased (HR = 0.62; 95% CI, 0.46-0.82) as well as a host of other secondary endpoints. This is not the only answer for patients that have mitral regurgitation and HF. These patients were carefully selected. They had to be managed medically and many of them do fine with that, but in a carefully conducted, rigorously presented trial, we were able to see a benefit. That’s a good thing for patients as a whole.

IMPERIAL

Chandan Devireddy

Devireddy: One of the top highlights of TCT is the IMPERIAL trial, which I think is setting a new standard for what will likely be our first-line choice for stent-based therapy for femoropopliteal lesions. Patients were randomly assigned to the Eluvia (Boston Scientific; n = 309) or Zilver PTX (Cook Medical; n = 156) stent and presented with lesions that probably are fairly close to what we see in the real world — a little longer than lesions we’ve seen in previous trials. The drug elution is the same, as far as the pharmacology is concerned; both are paclitaxel-eluting stents, but the Eluvia stent has a longer elution time, close to a full year, which likely may explain the differences seen in 12-month primary patency between these two stents (88.5% vs. 79.5%; P = .0119).

During TCT, the company announced that the FDA approved the Eluvia stent on the basis of this study. We will hopefully have this stent available to use for clinical use. I think these data support the use of it. We'll have to see longer-term studies in terms of secondary patency and rates of revascularization and whether there is a difference that persists between the two stents or whether it evens out long-term between both devices. But, overall, I think these data are a great win for the Eluvia stent.

SOLVE-TAVI

Molly Szerlip

Szerlip: SOLVE-TAVI was a well-done trial. In this study, 219 patients were assigned the self-expanding valve (CoreValve Evolut R, Medtronic) and 219 patients were assigned the balloon-expandable valve (Sapien 3, Edwards Lifesciences). Patients were also assigned to local (n = 218) or general anesthesia (n = 220). The primary endpoint for the valve strategy — all-cause mortality, stroke, permanent pacemaker implantation and either moderate or severe prosthetic valve regurgitation at 30 days — occurred in 27.2% of patients assigned to the self-expanding valve vs. 26.1% of those assigned to the balloon-expandable valve (rate difference = –1.14; 90% CI, –8.15 to 5.87; P for equivalence = .02; P for superiority = .83). The primary endpoint for the anesthesia strategy — all-cause mortality, stroke, MI, acute kidney injury and infection requiring antibiotic treatment at 30 days — was seen in 27% of patients in the local anesthesia group vs. 25.5% in the general anesthesia group (rate difference = –1.52; 90% CI, –8.47 to 5.42; P for equivalence = .02; P for superiority = .74).

We all would like to know if one type of valve is better than another (balloon expandable vs. self-expanding). In 80% or 90% of the cases, they are equal.

The answer to this question is still not known. We think that in some populations, one may be better than the other. As mentioned during the press conference by Michael J. Mack, MD, FACC, it is like a Venn diagram in the majority of populations, it probably does not matter.

For the general anesthesia vs. conscious sedation question, it is probably more important for us in the U.S than in Europe. In Europe, they do things a little bit differently as far as length of stay and other factors, but for us here in the U.S., length of stay is a big deal. A shorter length of stay, which usually occurs with local anesthesia, decreases cost.

This once again shows that there is no harm in using conscious sedation. In some cases, there may be better outcomes if you do conscious sedation because it decreases length of stay.

Thourani: It is refreshing to see randomized trials comparing one transcatheter valve to another. In Europe, a multitude of valves are commercially available. In the U.S., we only have two, so luckily, they chose the two valves that we have available. I imagine it was intentional.

What I take away from SOLVE-TAVI is that in experienced high-volume centers, the type of valve nor the procedure technique does not make a significant difference. Although this is overall an underpowered study, it does give comfort for those people using self-expanding valves and it gives comfort to those using balloon-expandable valves.

We have to be cautious about this being a small-powered study, but it showed no major difference between the valve types for the primary endpoint.

When you look at the individual components of it, mortality was not a difference. Stroke rate surprisingly was higher in the balloon-expandable valve, though the stroke rates associated with it in U.S. cohorts are lower.

As expected, the pacemaker rate was higher with the self-expanding valves. That was not a huge surprise, but it was surprising that the balloon-expandable valve had a higher pacemaker rate than what we had published in the past.

Vinod H. Thourani

There is an important difference between the current U.S. practice and what we saw with SOLVE-TAVI: The patient risk is higher than we are normally used to seeing. For instance, the Society of Thoracic Surgeons Predicted Risk of Mortality score was somewhere in the high 7% range. What we are seeing in the U.S. is somewhere around 4% to 5%. That is a higher-risk patient population than in the U.S.; the TVT registry population is best described as medium-risk.

As far as the paravalvular leak rate goes, that also was equivalent between the two, so that is something that was refreshing to see.

Even though now we are looking at this globally, we have to start homing in on which valve is better for what anatomical consideration. This study did not do that necessarily, but that is something that we have to dive into a little bit more.

When it comes to local anesthesia vs. general anesthesia, it was quite surprising that the length of time to do the procedure was not different between the two. You would think that with general anesthesia that it would take longer, but it did not.

It was quite refreshing to see that either technique works well in terms of the primary endpoints. Some reports have said that there is a higher paravalvular leakage rate with conscious sedation, but that was not really prevalent in this study.

At the end of the day, each operator should use the type of valve and the type of anesthesia technique they are most comfortable with.

Devireddy: This is a fascinating trial that probably raises more questions than it does answers.

Overall, as far as the primary outcome is concerned, the valves were essentially equivalent with the exception of a few endpoints. But from the standpoint of stroke there was a slightly higher risk for stroke with the use of the balloon-expandable valve, close to about 4%, which anecdotally I feel is much higher than our personal experience and higher than what we’ve seen in randomized trials specific to these individual platforms. From the standpoint of pacemaker use, for both products, the need for permanent pacemaker was also higher than what I would expect on the order of 19% to 22%. It would be interesting to get more information about who these patients were who needed pacemakers and why there might be this difference in both stroke and pacemaker rates between these trials and what we’ve seen in prior trials. The strong camps of users for both valves have data to suggest that their products are probably close to equivalent. We need longer-term data to see if there are any other differences that get teased out in the long term.

The other interesting aspect of that trial is that it was a 2x2 randomized trial, and there was also a comparison between local and general anesthesia. This part also showed equivalence in the primary outcome, but again with some differences. For ICU stay and length of stay overall, there appear to be trends and benefit toward local anesthesia. There were some differences in the individual care pathways for these patients, compared to what other centers may experience. The overall length of stay was longer and the use of the ICU was greater than what I might anticipate for the minimalist or local sedation kind of pathway. These data strongly suggest that local anesthesia/minimalist care pathways for TAVR is definitely no hazard compared with general anesthesia. If anything, there may be a benefit. There weren’t specific cost analyses provided but I think there would be an advantage in that.

LEADERS FREE II

Wilson: The biolimus stent used in the LEADERS FREE II trial (BioFreedom, Biosensors International) is an interesting stent. It is a little bit different because it is a drug-coated stent, but there is no polymer coating on the stent itself.

B. Hadley Wilson

In the LEADERS FREE II trial, 1,148 patients with high bleeding risk were compared with a propensity-matched cohort of bare-metal controls consisting of 1,189 patients. The primary safety endpoint — a composite of cardiac death and MI at 1 year — occurred in 12.3% of patients assigned the BMS vs. 8.6% assigned the drug-coated stent (risk difference = –3.7%; 95% CI, –6.6 to 1.4; HR = 0.67; 95% CI, 0.51-0.88; P for noninferiority < .0001; P for superiority = .0025). There was no significant difference in the secondary safety endpoints of all-cause death (P = .21), definite and probable stent thrombosis (P = .63), acute and subacute stent thrombosis (P = .87) and late stent thrombosis (P = .75).

The stent appears to be safe and to have advantages that so far we have not necessarily seen in other stents. The investigators were able to use only 30-day DAPT in the patients with high bleeding risk and still had great outcomes at 1 year for this stent. That is an advantage for patients who are on oral anticoagulation who are elderly, who have renal failure or who have previous bleeding conditions or the tendency to bleed. There were also good outcomes in terms of what we expect from other DES in terms of reduced re-narrowing or restenosis.

This is one of many second- and third-generation DES showing improved outcomes. The manufacturers are getting better with their strut thickness and design. It is very important that we know now that smaller struts are safer. Also, if we have less inflammatory response from the stent or the polymer, then that is safer too for patients. Finally, if that is true, then maybe we do not have to use DAPT as long, and therefore, we can use these stents in more patients.

This study gives good evidence that it is a safe stent that the FDA could approve to be in the armamentarium with other stents that are out there.

Why would someone use this stent? It is a safe and effective drug-coated stent for the general population, and may also even be better than other stents or at least it has evidence that it can be very safe in these high-bleeding-risk patients.

We see high bleeding risk quite a lot, particularly in the elderly. Atrial fibrillation is so prominent in all our populations and anticoagulation is so important to them, so if we can find stents that allows us to give fewer antithrombotic drugs, then hopefully patients can have their stent without the risk for increased bleeding.

The only other concern is that there was a little bit higher stent thrombosis rate than we are used to seeing, at the 1% range. Because he drug is applied directly on the stent with no polymer or anything to mete out the absorption over time — it is all gone within 30 days — that may be part of the reason that there was a higher stent thrombosis rate. That is something that is of concern and needs to be further looked into to make sure that the technology is safe.

Rao: The LEADERS FREE II trial is a very important study because we are starting to see these high-bleeding-risk patients more in our practice. The population is aging, and the comorbidities are going up. Many times, these patients are turned down for bypass surgery because of their comorbidities.

We need to see more studies that include those patients. That’s going to require a push on the clinical community, not industry because industry has obvious reservations about that. These patients die from all types of causes. As a clinical community, we’re going to have to push to do more studies in this population.

ULTIMATE

Kumbhani: ULTIMATE was a well-done multicenter trial. The investigators enrolled about 1,450 patients to test a hypothesis that using IVUS routinely for PCI was helpful compared with just using angiography.

Dharam J. Kumbhani

What was a little different about this trial was that there were very clear guidelines about what constituted “successful” PCI. Three criteria were listed. It is fairly prescriptive in the IVUS arm that if you did not meet the three criteria, then you had to keep going until you actually achieve that. That is probably an important distinction of this trial from others.

The researchers were able to show statistical superiority of an IVUS-guided strategy compared with angiography-based PCI for the primary endpoint of target vessel failure at 12 months (HR = 0.53; 95% CI, 0.312-0.901). Further, all of the endpoints trended in the right direction, particularly for the need for repeat revascularization, where the P value was .07.

Globally, this trial is consistent with many of the other recent trials that suggest that IVUS-guided PCI is helpful. What is different is the strict protocol that had to be followed in the IVUS group before completion of PCI, which may be a bit challenging logistically for all lesions in routine practice. Even in this trial, despite this requirement, only 60% of lesions successfully met all three criteria at the end for “optimal PCI.” Thus, a practice of IVUS-guided PCI may be higher yield for certain patients and lesions.

For example, most people who practice would agree that for left main PCI, they would use IVUS almost every single time. I do that as well. For complex thrombotic or calcified lesions, IVUS-guided PCI may be helpful too. Recent studies suggest that use of IVUS/OCT for PCI in the United States is still under 10%; we are thus likely underusing this helpful technology.

MAIN-COMPARE

Gibson: The MAIN-COMPARE trial does not feature randomized data. It is hard to draw conclusions. It can tell you about who is getting PCI or CABG, but it cannot really be used to compare the two techniques.

C. Michael Gibson

In this trial, 2,240 patients with unprotected left main CAD underwent either CABG (n = 1,138; mean age, 63 years; 73% men) or PCI (n = 1,102; mean age, 61 years; 71% men). During follow-up for a median of 12 years, the PCI and CABG groups had similar 10-year rates of death (21.1% vs. 23.2%, respectively; P = .23) and the composite of Q-wave MI, death or stroke (23.8% vs. 26.3%, respectively; P = .13). The PCI group had a consistently higher risk for target vessel revascularization compared with the CABG group (21.1% vs. 5.8%; P < .001).

OAC-ALONE

Gibson: The OAC-ALONE study was very provocative. Researchers analyzed 690 patients with concomitant AF and stable CAD who received a coronary stent. Patients were assigned either oral anticoagulation alone or a combination or oral anticoagulation and antiplatelet therapy. During a median follow-up of 2.5 years, the primary endpoint — a composite of MI, all-cause death, systemic embolism or stroke — occurred in more patients in the oral anticoagulation alone group vs. the combined therapy group (15.7% vs. 13.6%), and noninferiority was not met (HR = 1.16; 95% CI, 0.79-1.72; P for noninferiority = .2; P for superiority = .45). The rate of the major secondary endpoint, the primary endpoint plus major bleeding, was similar in the oral anticoagulation alone group and the combined therapy group (19.5% vs. 19.4%, respectively), and noninferiority was met (HR = 0.99; 95% CI, 0.71-1.39; P for noninferiority = .016; P for superiority = .96).

It is unclear what to do after a year, so this was useful in that regard. It was one of the bigger randomized studies looking at this issue; however, I really want to know what the modest bleeding and major bleeding rates were. People make decisions based also upon smaller bleeds.

The study does not show any big benefit of continuing antiplatelet therapy beyond 1 year, which may not be all that surprising.

David E. Kandzari

BIOFLOW-V

Kandzari: For the BIOFLOW-V trial, my colleagues and I assigned 1,334 patients with CAD who underwent PCI either an ultrathin, bioresorbable polymer sirolimus-eluting stent (Orsiro, Biotronik) or a thin, durable polymer everolimus-eluting stent (Xience, Abbott Vascular). At 2 years, patients assigned SES had a lower rate of TLF compared with those assigned EES (7.5% vs. 11.9%; P = .015), which resulted in a treatment difference of –4.33% (95% CI, –8.16 to –0.91). This was driven by significant differences in ischemia-driven TLR (2.6% vs. 4.9%; P = .04) and target vessel-related MI (5.3% vs. 9.5%; P = .01). The SES group had a lower incidence of cardiac death or MI compared with the EES group (7% vs. 10.4%; P = .047), in addition to lower combined late and very late rates of definite and definite/probable stent thrombosis (0.1% vs. 1%; P = .045).

This study was the first time in a large comparative randomized trial that we observed a significant difference that favored superiority for a newer stent type compared with the Xience stent, which has historically been a benchmark of comparison.

The regulatory requirement by the FDA for approval of DES in the United States is to perform large randomized trials and ideally, international trials for broad experience. One motivation was to bring this stent and its clinical promise to the United States for commercial availability and for physicians to use for their patients.

The Orsiro stent differs from the Xience stent not only that it has a bioresorbable polymer that dissolves over time compared with a permanent durable polymer of the Xience stent, but the Orsiro stent is an ultrathin-strut stent. It has a stent strut thickness of 60 µm compared with 81 µm for the Xience permanent polymer DES.

Outcomes with contemporary DES are so favorable today that it’s been so challenging to demonstrate iterative improvement in the context of very low frequency event rates, but now these results establish a new standard for comparison.

Renal denervation

Devireddy: A major highlight from TCT was the excitement and interest that is burgeoning again behind the field of renal denervation and sympathetic modulation for the treatment of high BP. There are large-scale trials that have generated excitement and buzz about renal denervation years ago, but the publication of the SYMPLICITY HTN-3 trial had taken a lot of the wind out of the sails for that interest in renal denervation. As of this meeting, we now have a solid mass of data that show us that at least we have to answer this question. In RADIOSOUND-HTN, presented here, 120 patients with resistant hypertension despite taking at least three BP medications had decreases in daytime systolic and diastolic BP at 3 months of 9.5/6.3 mm Hg (P for both < .001), though those who had ultrasound ablation had better results than those who had radiofrequency ablation.

That has been apparent at this meeting; there has been a lot of interest, further data and questions about where do we move forward. Is there a potential regulatory pathway that may be coming for renal denervation in the next year or two? Based on what we have seen at this meeting, I think there’s a lot more to expect from that field over the next year or two.

Disclosures: Devireddy reports he consults for Medtronic, ReCor Medical and Vascular Dynamics. Gibson reports he is CEO of the Baim Institute, a nonprofit organization which receives research grant support from device manufacturers, and receives research grant support from all major manufacturers of antiplatelet and antithrombotic therapies. Kandzari reports he received institutional research/grant support from Biotronik, Boston Scientific, Medinol, Medtronic and OrbusNeich and personal consultant honoraria from Boston Scientific, Cardiovascular Systems and Medtronic. Kirtane reports he receives institutional funding to Columbia University and/or Cardiovascular Research Foundation from Abbott Vascular, Abiomed, Boston Scientific, CathWorks, CSI, Medtronic, Philips, ReCor Medical and Siemens. Kumbhani, Szerlip and Wilson report no relevant financial disclosures. Rao reports he was on the steering committee for the LEADERS FREE II trial. Thourani reports he has relationships with Abbott Vascular, Boston Scientific, Edwards Lifesciences, Gore Vascular, JenaValve and Medtronic.

The annual Transcatheter Cardiovascular Therapeutics Scientific Symposium, held Sept. 21 to 25 in San Diego, brought many of interventional cardiology’s hottest topics to the forefront.

Cardiology Today’s Intervention was on-site and spoke with experts for their perspective on the top research presented at this year’s meeting. Those who provided their opinion included Chandan Devireddy, MD, FACC, FSCAI, from Emory University; C. Michael Gibson, MD, MS, from Harvard Medical School and Beth Israel Deaconess Medical Center; David E. Kandzari, MD, from Piedmont Heart Institute; Cardiology Today’s Intervention Editorial Board Member Ajay Kirtane, MD, SM, from NewYork-Presbyterian Hospital/Columbia University Irving Medical Center; Dharam J. Kumbhani, MD, SM, from UTSouthwestern Medical Center; Cardiology Today’s Intervention Editorial Board Member Sunil V. Rao, MD, from Duke University Health System; Molly Szerlip, MD, FACC, FACP, FSCAI, from Baylor Scott and White The Heart Hospital – Plano; Vinod H. Thourani, MD, FACS, FACC, from MedStar Heart and Vascular Institute; and B. Hadley Wilson, MD, FACC, from Atrium Health and the University of North Carolina School of Medicine.

COAPT

Ajay Kirtane

Kirtane: We heard the results of the COAPT trial. It’s pretty amazing to see results like this, where you see not only reductions in terms of hospitalizations for HF (HR = 0.53; 95% CI, 0.4-0.7) in these 614 patients that have HF with mitral regurgitation treated with MitraClip (Abbott), but also an endpoint of all-cause mortality being decreased (HR = 0.62; 95% CI, 0.46-0.82) as well as a host of other secondary endpoints. This is not the only answer for patients that have mitral regurgitation and HF. These patients were carefully selected. They had to be managed medically and many of them do fine with that, but in a carefully conducted, rigorously presented trial, we were able to see a benefit. That’s a good thing for patients as a whole.

IMPERIAL

Chandan Devireddy

Devireddy: One of the top highlights of TCT is the IMPERIAL trial, which I think is setting a new standard for what will likely be our first-line choice for stent-based therapy for femoropopliteal lesions. Patients were randomly assigned to the Eluvia (Boston Scientific; n = 309) or Zilver PTX (Cook Medical; n = 156) stent and presented with lesions that probably are fairly close to what we see in the real world — a little longer than lesions we’ve seen in previous trials. The drug elution is the same, as far as the pharmacology is concerned; both are paclitaxel-eluting stents, but the Eluvia stent has a longer elution time, close to a full year, which likely may explain the differences seen in 12-month primary patency between these two stents (88.5% vs. 79.5%; P = .0119).

PAGE BREAK

During TCT, the company announced that the FDA approved the Eluvia stent on the basis of this study. We will hopefully have this stent available to use for clinical use. I think these data support the use of it. We'll have to see longer-term studies in terms of secondary patency and rates of revascularization and whether there is a difference that persists between the two stents or whether it evens out long-term between both devices. But, overall, I think these data are a great win for the Eluvia stent.

SOLVE-TAVI

Molly Szerlip

Szerlip: SOLVE-TAVI was a well-done trial. In this study, 219 patients were assigned the self-expanding valve (CoreValve Evolut R, Medtronic) and 219 patients were assigned the balloon-expandable valve (Sapien 3, Edwards Lifesciences). Patients were also assigned to local (n = 218) or general anesthesia (n = 220). The primary endpoint for the valve strategy — all-cause mortality, stroke, permanent pacemaker implantation and either moderate or severe prosthetic valve regurgitation at 30 days — occurred in 27.2% of patients assigned to the self-expanding valve vs. 26.1% of those assigned to the balloon-expandable valve (rate difference = –1.14; 90% CI, –8.15 to 5.87; P for equivalence = .02; P for superiority = .83). The primary endpoint for the anesthesia strategy — all-cause mortality, stroke, MI, acute kidney injury and infection requiring antibiotic treatment at 30 days — was seen in 27% of patients in the local anesthesia group vs. 25.5% in the general anesthesia group (rate difference = –1.52; 90% CI, –8.47 to 5.42; P for equivalence = .02; P for superiority = .74).

We all would like to know if one type of valve is better than another (balloon expandable vs. self-expanding). In 80% or 90% of the cases, they are equal.

The answer to this question is still not known. We think that in some populations, one may be better than the other. As mentioned during the press conference by Michael J. Mack, MD, FACC, it is like a Venn diagram in the majority of populations, it probably does not matter.

For the general anesthesia vs. conscious sedation question, it is probably more important for us in the U.S than in Europe. In Europe, they do things a little bit differently as far as length of stay and other factors, but for us here in the U.S., length of stay is a big deal. A shorter length of stay, which usually occurs with local anesthesia, decreases cost.

This once again shows that there is no harm in using conscious sedation. In some cases, there may be better outcomes if you do conscious sedation because it decreases length of stay.

Thourani: It is refreshing to see randomized trials comparing one transcatheter valve to another. In Europe, a multitude of valves are commercially available. In the U.S., we only have two, so luckily, they chose the two valves that we have available. I imagine it was intentional.

What I take away from SOLVE-TAVI is that in experienced high-volume centers, the type of valve nor the procedure technique does not make a significant difference. Although this is overall an underpowered study, it does give comfort for those people using self-expanding valves and it gives comfort to those using balloon-expandable valves.

PAGE BREAK

We have to be cautious about this being a small-powered study, but it showed no major difference between the valve types for the primary endpoint.

When you look at the individual components of it, mortality was not a difference. Stroke rate surprisingly was higher in the balloon-expandable valve, though the stroke rates associated with it in U.S. cohorts are lower.

As expected, the pacemaker rate was higher with the self-expanding valves. That was not a huge surprise, but it was surprising that the balloon-expandable valve had a higher pacemaker rate than what we had published in the past.

Vinod H. Thourani

There is an important difference between the current U.S. practice and what we saw with SOLVE-TAVI: The patient risk is higher than we are normally used to seeing. For instance, the Society of Thoracic Surgeons Predicted Risk of Mortality score was somewhere in the high 7% range. What we are seeing in the U.S. is somewhere around 4% to 5%. That is a higher-risk patient population than in the U.S.; the TVT registry population is best described as medium-risk.

As far as the paravalvular leak rate goes, that also was equivalent between the two, so that is something that was refreshing to see.

Even though now we are looking at this globally, we have to start homing in on which valve is better for what anatomical consideration. This study did not do that necessarily, but that is something that we have to dive into a little bit more.

When it comes to local anesthesia vs. general anesthesia, it was quite surprising that the length of time to do the procedure was not different between the two. You would think that with general anesthesia that it would take longer, but it did not.

It was quite refreshing to see that either technique works well in terms of the primary endpoints. Some reports have said that there is a higher paravalvular leakage rate with conscious sedation, but that was not really prevalent in this study.

At the end of the day, each operator should use the type of valve and the type of anesthesia technique they are most comfortable with.

Devireddy: This is a fascinating trial that probably raises more questions than it does answers.

PAGE BREAK

Overall, as far as the primary outcome is concerned, the valves were essentially equivalent with the exception of a few endpoints. But from the standpoint of stroke there was a slightly higher risk for stroke with the use of the balloon-expandable valve, close to about 4%, which anecdotally I feel is much higher than our personal experience and higher than what we’ve seen in randomized trials specific to these individual platforms. From the standpoint of pacemaker use, for both products, the need for permanent pacemaker was also higher than what I would expect on the order of 19% to 22%. It would be interesting to get more information about who these patients were who needed pacemakers and why there might be this difference in both stroke and pacemaker rates between these trials and what we’ve seen in prior trials. The strong camps of users for both valves have data to suggest that their products are probably close to equivalent. We need longer-term data to see if there are any other differences that get teased out in the long term.

The other interesting aspect of that trial is that it was a 2x2 randomized trial, and there was also a comparison between local and general anesthesia. This part also showed equivalence in the primary outcome, but again with some differences. For ICU stay and length of stay overall, there appear to be trends and benefit toward local anesthesia. There were some differences in the individual care pathways for these patients, compared to what other centers may experience. The overall length of stay was longer and the use of the ICU was greater than what I might anticipate for the minimalist or local sedation kind of pathway. These data strongly suggest that local anesthesia/minimalist care pathways for TAVR is definitely no hazard compared with general anesthesia. If anything, there may be a benefit. There weren’t specific cost analyses provided but I think there would be an advantage in that.

LEADERS FREE II

Wilson: The biolimus stent used in the LEADERS FREE II trial (BioFreedom, Biosensors International) is an interesting stent. It is a little bit different because it is a drug-coated stent, but there is no polymer coating on the stent itself.

B. Hadley Wilson

In the LEADERS FREE II trial, 1,148 patients with high bleeding risk were compared with a propensity-matched cohort of bare-metal controls consisting of 1,189 patients. The primary safety endpoint — a composite of cardiac death and MI at 1 year — occurred in 12.3% of patients assigned the BMS vs. 8.6% assigned the drug-coated stent (risk difference = –3.7%; 95% CI, –6.6 to 1.4; HR = 0.67; 95% CI, 0.51-0.88; P for noninferiority < .0001; P for superiority = .0025). There was no significant difference in the secondary safety endpoints of all-cause death (P = .21), definite and probable stent thrombosis (P = .63), acute and subacute stent thrombosis (P = .87) and late stent thrombosis (P = .75).

The stent appears to be safe and to have advantages that so far we have not necessarily seen in other stents. The investigators were able to use only 30-day DAPT in the patients with high bleeding risk and still had great outcomes at 1 year for this stent. That is an advantage for patients who are on oral anticoagulation who are elderly, who have renal failure or who have previous bleeding conditions or the tendency to bleed. There were also good outcomes in terms of what we expect from other DES in terms of reduced re-narrowing or restenosis.

PAGE BREAK

This is one of many second- and third-generation DES showing improved outcomes. The manufacturers are getting better with their strut thickness and design. It is very important that we know now that smaller struts are safer. Also, if we have less inflammatory response from the stent or the polymer, then that is safer too for patients. Finally, if that is true, then maybe we do not have to use DAPT as long, and therefore, we can use these stents in more patients.

This study gives good evidence that it is a safe stent that the FDA could approve to be in the armamentarium with other stents that are out there.

Why would someone use this stent? It is a safe and effective drug-coated stent for the general population, and may also even be better than other stents or at least it has evidence that it can be very safe in these high-bleeding-risk patients.

We see high bleeding risk quite a lot, particularly in the elderly. Atrial fibrillation is so prominent in all our populations and anticoagulation is so important to them, so if we can find stents that allows us to give fewer antithrombotic drugs, then hopefully patients can have their stent without the risk for increased bleeding.

The only other concern is that there was a little bit higher stent thrombosis rate than we are used to seeing, at the 1% range. Because he drug is applied directly on the stent with no polymer or anything to mete out the absorption over time — it is all gone within 30 days — that may be part of the reason that there was a higher stent thrombosis rate. That is something that is of concern and needs to be further looked into to make sure that the technology is safe.

Rao: The LEADERS FREE II trial is a very important study because we are starting to see these high-bleeding-risk patients more in our practice. The population is aging, and the comorbidities are going up. Many times, these patients are turned down for bypass surgery because of their comorbidities.

We need to see more studies that include those patients. That’s going to require a push on the clinical community, not industry because industry has obvious reservations about that. These patients die from all types of causes. As a clinical community, we’re going to have to push to do more studies in this population.

ULTIMATE

Kumbhani: ULTIMATE was a well-done multicenter trial. The investigators enrolled about 1,450 patients to test a hypothesis that using IVUS routinely for PCI was helpful compared with just using angiography.

Dharam J. Kumbhani

What was a little different about this trial was that there were very clear guidelines about what constituted “successful” PCI. Three criteria were listed. It is fairly prescriptive in the IVUS arm that if you did not meet the three criteria, then you had to keep going until you actually achieve that. That is probably an important distinction of this trial from others.

The researchers were able to show statistical superiority of an IVUS-guided strategy compared with angiography-based PCI for the primary endpoint of target vessel failure at 12 months (HR = 0.53; 95% CI, 0.312-0.901). Further, all of the endpoints trended in the right direction, particularly for the need for repeat revascularization, where the P value was .07.

PAGE BREAK

Globally, this trial is consistent with many of the other recent trials that suggest that IVUS-guided PCI is helpful. What is different is the strict protocol that had to be followed in the IVUS group before completion of PCI, which may be a bit challenging logistically for all lesions in routine practice. Even in this trial, despite this requirement, only 60% of lesions successfully met all three criteria at the end for “optimal PCI.” Thus, a practice of IVUS-guided PCI may be higher yield for certain patients and lesions.

For example, most people who practice would agree that for left main PCI, they would use IVUS almost every single time. I do that as well. For complex thrombotic or calcified lesions, IVUS-guided PCI may be helpful too. Recent studies suggest that use of IVUS/OCT for PCI in the United States is still under 10%; we are thus likely underusing this helpful technology.

MAIN-COMPARE

Gibson: The MAIN-COMPARE trial does not feature randomized data. It is hard to draw conclusions. It can tell you about who is getting PCI or CABG, but it cannot really be used to compare the two techniques.

C. Michael Gibson

In this trial, 2,240 patients with unprotected left main CAD underwent either CABG (n = 1,138; mean age, 63 years; 73% men) or PCI (n = 1,102; mean age, 61 years; 71% men). During follow-up for a median of 12 years, the PCI and CABG groups had similar 10-year rates of death (21.1% vs. 23.2%, respectively; P = .23) and the composite of Q-wave MI, death or stroke (23.8% vs. 26.3%, respectively; P = .13). The PCI group had a consistently higher risk for target vessel revascularization compared with the CABG group (21.1% vs. 5.8%; P < .001).

OAC-ALONE

Gibson: The OAC-ALONE study was very provocative. Researchers analyzed 690 patients with concomitant AF and stable CAD who received a coronary stent. Patients were assigned either oral anticoagulation alone or a combination or oral anticoagulation and antiplatelet therapy. During a median follow-up of 2.5 years, the primary endpoint — a composite of MI, all-cause death, systemic embolism or stroke — occurred in more patients in the oral anticoagulation alone group vs. the combined therapy group (15.7% vs. 13.6%), and noninferiority was not met (HR = 1.16; 95% CI, 0.79-1.72; P for noninferiority = .2; P for superiority = .45). The rate of the major secondary endpoint, the primary endpoint plus major bleeding, was similar in the oral anticoagulation alone group and the combined therapy group (19.5% vs. 19.4%, respectively), and noninferiority was met (HR = 0.99; 95% CI, 0.71-1.39; P for noninferiority = .016; P for superiority = .96).

It is unclear what to do after a year, so this was useful in that regard. It was one of the bigger randomized studies looking at this issue; however, I really want to know what the modest bleeding and major bleeding rates were. People make decisions based also upon smaller bleeds.

PAGE BREAK

The study does not show any big benefit of continuing antiplatelet therapy beyond 1 year, which may not be all that surprising.

David E. Kandzari

BIOFLOW-V

Kandzari: For the BIOFLOW-V trial, my colleagues and I assigned 1,334 patients with CAD who underwent PCI either an ultrathin, bioresorbable polymer sirolimus-eluting stent (Orsiro, Biotronik) or a thin, durable polymer everolimus-eluting stent (Xience, Abbott Vascular). At 2 years, patients assigned SES had a lower rate of TLF compared with those assigned EES (7.5% vs. 11.9%; P = .015), which resulted in a treatment difference of –4.33% (95% CI, –8.16 to –0.91). This was driven by significant differences in ischemia-driven TLR (2.6% vs. 4.9%; P = .04) and target vessel-related MI (5.3% vs. 9.5%; P = .01). The SES group had a lower incidence of cardiac death or MI compared with the EES group (7% vs. 10.4%; P = .047), in addition to lower combined late and very late rates of definite and definite/probable stent thrombosis (0.1% vs. 1%; P = .045).

This study was the first time in a large comparative randomized trial that we observed a significant difference that favored superiority for a newer stent type compared with the Xience stent, which has historically been a benchmark of comparison.

The regulatory requirement by the FDA for approval of DES in the United States is to perform large randomized trials and ideally, international trials for broad experience. One motivation was to bring this stent and its clinical promise to the United States for commercial availability and for physicians to use for their patients.

The Orsiro stent differs from the Xience stent not only that it has a bioresorbable polymer that dissolves over time compared with a permanent durable polymer of the Xience stent, but the Orsiro stent is an ultrathin-strut stent. It has a stent strut thickness of 60 µm compared with 81 µm for the Xience permanent polymer DES.

Outcomes with contemporary DES are so favorable today that it’s been so challenging to demonstrate iterative improvement in the context of very low frequency event rates, but now these results establish a new standard for comparison.

PAGE BREAK

Renal denervation

Devireddy: A major highlight from TCT was the excitement and interest that is burgeoning again behind the field of renal denervation and sympathetic modulation for the treatment of high BP. There are large-scale trials that have generated excitement and buzz about renal denervation years ago, but the publication of the SYMPLICITY HTN-3 trial had taken a lot of the wind out of the sails for that interest in renal denervation. As of this meeting, we now have a solid mass of data that show us that at least we have to answer this question. In RADIOSOUND-HTN, presented here, 120 patients with resistant hypertension despite taking at least three BP medications had decreases in daytime systolic and diastolic BP at 3 months of 9.5/6.3 mm Hg (P for both < .001), though those who had ultrasound ablation had better results than those who had radiofrequency ablation.

That has been apparent at this meeting; there has been a lot of interest, further data and questions about where do we move forward. Is there a potential regulatory pathway that may be coming for renal denervation in the next year or two? Based on what we have seen at this meeting, I think there’s a lot more to expect from that field over the next year or two.

Disclosures: Devireddy reports he consults for Medtronic, ReCor Medical and Vascular Dynamics. Gibson reports he is CEO of the Baim Institute, a nonprofit organization which receives research grant support from device manufacturers, and receives research grant support from all major manufacturers of antiplatelet and antithrombotic therapies. Kandzari reports he received institutional research/grant support from Biotronik, Boston Scientific, Medinol, Medtronic and OrbusNeich and personal consultant honoraria from Boston Scientific, Cardiovascular Systems and Medtronic. Kirtane reports he receives institutional funding to Columbia University and/or Cardiovascular Research Foundation from Abbott Vascular, Abiomed, Boston Scientific, CathWorks, CSI, Medtronic, Philips, ReCor Medical and Siemens. Kumbhani, Szerlip and Wilson report no relevant financial disclosures. Rao reports he was on the steering committee for the LEADERS FREE II trial. Thourani reports he has relationships with Abbott Vascular, Boston Scientific, Edwards Lifesciences, Gore Vascular, JenaValve and Medtronic.